Ozempic: Miracle Drug or Ticking Time-Bomb?

A lot of podcasters have recently started discussing the benefits of Ozempic and other GLP-1 Receptor Agonists. Are they worth the risk?

Photo by i yunmai on Unsplash

Background

I was listening to a recent episode of the Modern Wisdom podcast in which Chris (the host) discusses the investigation and experience of Johann Hari with the increasingly popular “weight-loss” drug Ozempic. Generically known as semaglutide, a GLP-1 receptor agonist.

I wanted to hear what Hari had to say, because in the past I appreciated the sobering perspective he provided on depression and antidepressants. I came away from it with a tenuously positive impression of his thought process and rigor.

Fast-forward to 2024, he has a new book concerning the miracle weight-loss drug Ozempic. In the podcast with Chris, he describes first encountering Ozempic amongst the Hollywood elite who had miraculously lost weight during covid-era lockdowns. He described them as gaunt - an adjective meaning lean, bony, and emaciated.

Given his initial impression about the way in which the users of Ozempic looked, Hari decided to investigate and experiment with it. Despite all that he has learned and experienced, he is surprisingly still on the drug. More on why, later.

Ozempic

GLP-1 receptor agonists (RAs) were initially introduced to the market in the 2000s as a drug to help improve the insulin response of diabetics. One of the observed effects is to heighten the release of insulin to improve the control of serum blood sugar. It was initially believed that diabetics were deficient in GLP-1, but subsequent analysis has revealed that is not entirely true.

Interestingly, most people with diabetes have a similar GLP-1 response as those without diabetes. Negating the claim that its effect is by modulating insulin release. However, there is a population for whom the claim turned out to be true. Specifically, older/fatter people with long-standing and poorly controlled diabetes.

One of the interesting effects that have been observed, however, has been weight loss. What is clear now, and what Hari talks about extensively, is the impact of drugs like Ozempic on increasing satiety. In other words, profoundly suppressing your appetite.

No appetite → no food → “weight” loss.

Worth noting, however, that weight loss doesn’t necessarily mean fat loss. Which is what most are concerned with.

There are increasing reports from fitness and health gurus that Ozempic is actually causing muscle and water loss, in addition to fat loss. This has concerning implications in itself.

The claim that Ozempic impacts satiety is now far more believable, as GLP-1 is also found in the part of the brainstem which interfaces with our digestive tract as well as food-seeking and reward behavior centers of the brain. Even more fascinating, and related to this newly discovered phenomenon, Hari mentions that those who take Ozempic also find it helps to quit certain addictions, like alcohol and gambling.

As you can see, what began as a drug marketed simply for insulin modulation has evolved into something that is far more systemic than we had thought. With these systemic effects, there will also be consequences.

Before we get to the risks, let’s dig a little deeper into how it works and why it may be desired.

How It Works (?)

Photo by Aziz Acharki on Unsplash

As we’ve discussed, there are many paths for the effects of GLP-1RAs like Ozempic.

Let’s take at face value the claim from Hari that it is an inhibitor of appetite. Fine.

But, what else is it doing?

One paper looked at the impact of GLP-1RAs on inflammatory stress, oxidative balance and function/efficiency of mitochondria.

They conclude that:

GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.

Here, we can surmise that one of the ways in which it is improving our food-seeking behavior is by optimizing the function of our mitochondria, which are the energy-generating metabolic centers of the body.

Surely, this is a good thing?

If we are to take this effect in isolation, it is a good thing. Improved efficiency and function of mitochondria means we can metabolize energy supplies more effectively (reduced weight gain) and reduce the need for more calories.

But, we need to consider the picture as a whole.

Who is taking this drug? Why are they taking this drug? What physiologic baggage are they bringing to the table?

Concerns & Risks

To understand the risks, we first need to understand the needs of those who take this drug.